Members of the herpesviridae family are enveloped, double-stranded DNA viruses with relatively large complex genomes. At least 8 human herpesviruses have been identified, including human herpesvirus 1,2 (HSV-1, HSV-2), varicellovirus (VZV) or human herpesvirus 3, cytomegalovirus (CMV) or human herpesvirus 5, roseolovirus or human herpesvirus 6,7 (HHV-6, HHV-7), lymphocryptovirus (Epstein-Barr virus or EBV) or human herpesvirus 4, and rhadinovirus or human herpesvirus 8. These viruses are implicated in a number of human diseases such as facial or genital lesions and lynphotropic conditions. Human herpesvirus infections are endemic, and sexual contact is a significant method of transmission for several herpesviruses including herpes simplex virus 1 and 2, human CMV and likely Karposi's sarcoma herpesvirus. Prevalence of genetial herpes and corresponding rise of neonatal infection have implicated Epstein-Barr virus and Karposi's sarcoma herpesvirus as cofactors in human cancers.
Among herpesviruses, human CMV is a significant opportunistic pathogen responsible for serious clinical consequences in a variety of human subjects. Human subjects affected by CMV include immunosuppressed patient groups such as neonate and infants, persons with AIDS and individuals undergoing immunosuppressive regimes for the purpose of organ or bone marrow transplantation. Like other human herpesviruses, CMV establishes a life-long latent infection with its human host and is ubiquitous in the population with upwards of 75% infectivity rate found in the United States.
The currently available drugs for treating infections of herpesviruses are not very satisfactory due to various reasons. There is a need in the art to identify alternative drug targets and better agents to treat diseases and conditions associated with herpesviruses, e.g., CMV infection. The instant invention fulfills this and other needs.